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Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression: a hybridization study using two
1King Saud University, College of Medicine, Department of Anatomy, Abha, Saudi Arabia. A03A002@KSU.EDU.SA
Abstract:
The density and distribution of N-methyl-D-aspartate receptor (NMDAR1) mRNA expression in the rat midbrain Periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation or chronic constrictive injury (CCI) as models for chronic peripheral nociception were examined using the in situ hybridization technique. The NMDAR1 hybridization signal intensities increased significantly in the ventrolateral areas of the caudal and middle thirds of the PAG after 3 days of Complete Freund's Adjuvant (CFA) injection. Likewise, rats subjected to CCI showed significant increases in hybridization signal intensities in comparison to sham operated animals in both the ipsi and contra-lateral ventrolateral quadrants of the caudal and middle thirds of the PAG. In the caudal dorsal raphe, the CFA and the CCI treated animals showed a significant increase in signal hybridization compared to control and sham operated groups while the rostral dorsal raphe showed no significant changes in either CCI or CFA treated groups. In contrast, there was no significant change in signal intensity of NMDAR1 mRNA in the dorsal subdivisions of the PAG following either CCI or CFA treatment. These results demonstrate significant bilateral increase in NMDAR1 mRNA expression in the ventrolateral areas of the caudal and middle thirds of the PAG and the caudal half of the dorsal raphe following chronic nociception. The up-regulation phenomenon may constitute a reactive mechanism against chronic neuropathic pain in the PAG.
Insights
Chronic pain conditions, such as peripheral inflammation and nerve injury, increase N-methyl-D-aspartate receptor (NMDAR1) mRNA in specific brain regions. This up-regulation in the periaqueductal gray (PAG) may be a response to neuropathic pain.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Chronic pain, including neuropathic pain, involves complex changes in the central nervous system.
- N-methyl-D-aspartate receptors (NMDAR1) play a crucial role in pain signaling and plasticity.
- The periaqueductal gray (PAG) is a key midbrain structure involved in pain modulation.
Purpose of the Study:
- To investigate the expression and distribution of NMDAR1 mRNA in the rat PAG.
- To examine changes in NMDAR1 mRNA following models of chronic peripheral nociception.
- To determine if NMDAR1 up-regulation in the PAG is associated with chronic pain states.
Main Methods:
- In situ hybridization technique was used to detect NMDAR1 mRNA.
- Rats were exposed to unilateral peripheral inflammation (Complete Freund's Adjuvant - CFA) or chronic constrictive injury (CCI).
- NMDAR1 hybridization signal intensities were quantified in different PAG subdivisions.
Main Results:
- Significant bilateral increase in NMDAR1 mRNA expression was observed in the ventrolateral PAG (caudal and middle thirds) after CFA injection and CCI.
- Increased NMDAR1 mRNA was also found in the caudal dorsal raphe in both CFA and CCI groups.
- No significant changes in NMDAR1 mRNA were detected in the rostral dorsal raphe or dorsal PAG subdivisions.
Conclusions:
- Chronic nociception leads to a significant bilateral up-regulation of NMDAR1 mRNA in specific PAG areas and the caudal dorsal raphe.
- This up-regulation of NMDAR1 mRNA in the PAG may represent a compensatory mechanism against chronic neuropathic pain.
- Findings highlight the role of NMDAR1 in the PAG's response to sustained pain stimuli.
